Synthetic materials intended for bone void filling have been a topic of research interest for several years and there are many potential and important applications for such materials, including, among others, the filling of voids due to osteosarcoma and trauma. The gold standard in practice today, autologous bone, has disadvantages in its limited availability and in the risk of resistant pain. To overcome such drawbacks associated with the use of autologous bone, synthetic materials have become an important substitute. Calcium phosphate ceramics are one of the main groups of synthetic materials used in these applications and they advantageously combine biodegradation and biocompatibility. The calcium phosphate ceramics have the advantage of a chemical composition similar to the mineral phase of bone, i.e., ion-substituted calcium-deficient hydroxyapatite.
Calcium phosphate (CaP) materials for bone void filling applications are provided in many physical forms including premade scaffolds, granules, putties and self-setting cements. CaPs that are produced through a low temperature method, i.e., through a cement dissolution-precipitation reaction, are known as chemically bonded ceramic materials and have an entangled network of small crystallites. The small size of the crystallites makes the calcium phosphate cements (CPCs) degrade more rapidly than scaffolds prepared through a high temperature sintering process where larger and more compact crystals are formed.
It is highly desirable for a bone void-filling material to have a fast resorption rate, mirroring an equally fast formation of new bone. Resorbable CaP implants should work as a template for new bone formation and prevent the formation of fibrotic tissue within a bone void, rather than being a permanent bone substitute, similar to the manner in which autologous bone functions. To increase the bone ingrowth in synthetic bone void fillers, it has been suggested, and tested with good results, that the introduction of macropores could be helpful. Two main mechanisms are responsible for the bone ingrowth into bone void fillers. The first is osteoclastic degradation, similar to the normal remodelling mechanism of bone, and the second is resorption through dissolution of the material. Although the CPC based bone void fillers have a high inherent porosity, the pore size mainly lies in the vicinity of 1 μm and lower. An increased amount of macropores, i.e., pores having a size greater than 10 μm, as well as an increased interconnectivity of pores, could improve the cell colonization within the material and increase the osteoclastic degradation. Studies have shown that pore sizes greater than 100 μm are required for a good bone ingrowth, while sizes greater than 300 μm are recommended to achieve enhanced capillary and bone formation. See Karageorgiou et al, Biomaterials, 26:5474-91 (2005).
Macroporous cements can be either injected into a bone void and set in situ or hardened outside the body into a desired shape, normally into a granule shape, and used as an in vitro scaffold or an implant. The introduction of macropores into a cement has conventionally been performed through several routes. One method employs a mixture of the cement phase with a sacrifying phase (normally a sugar), which is dissolved after cement setting, thereby creating voids. Another method incorporates a surfactant to entrap air during cement mixing (see Sarda et al, Journal of Biomedical Materials Research Part A; 65A:215-21 (2003). Mechanical foaming of the cement paste is also used (see Ginebra et al, Journal of Biomedical Materials Research Part A, 80A:351-61 (2007); Perut et al, Acta Biomaterialia, 7:1780-7 (2011); Montufar et al, Journal of Materials Science: Materials in Medicine, 21:863-9 (2010)). The two main approaches, however, are the use of a sacrifying phase and mechanical foaming. The drawback with these conventional methods is the difficulty to achieve a controlled pore size distribution and interconnectivity, i.e., interconnection of pores. Although foaming could give a controlled distribution of pores in the foam through a rigorously-controlled foaming procedure, the foams are easily ruptured and distorted during cement setting and assuring an even distribution of pores in the final product is difficult. The use of a sugar as a sacrifying phase also has several disadvantages. Mainly, the fast dissolution of the sugars often causes dissolution before the setting of the cement has started, affecting the cement setting mechanism and creating unpredictable pore sizes and distribution. The sugars are furthermore hard to mold into desired shapes, limiting the size and shape of the sacrifying phase.
Accordingly, new methods for forming porous ceramic shaped articles are needed, and, additionally, new methods for forming porous ceramic shaped articles having macropores suitable for use as implants which avoid drawbacks of the prior art are needed.